Dan Med J 60/8 August 2013
Evaluation of cervical lymphadenopathy in children:
advantages and drawbacks of diagnostic methods
Maria Ingolfsdottir, Viggo Balle & Christoffer Holst Hahn
ABSTRACT
INTRODUCTION: Cervical lymphadenopathy (LAP) in chil
dren is a common clinical diagnostic dilemma. The aim of
our study was to analyse ultrasonography, fine needle as
piration biopsy, size and location on the neck to distinguish
lymph nodes requiring excision from those that do not.
MATERIAL AND METHODS: We retrospectively studied 43
cervical lymph nodes that were excised from 43 children
aged 0-16 years. We studied the histology of the removed
lymph nodes and compared them in terms of size, location,
ultrasonography and fine needle aspiration biopsy. Patients
were divided into four groups: reactive, malignant, granu
loma and other.
RESULTS: The cause of LAP was reactive in 30 patients
(70%), malignant in five (12%) and granulomatous in six
(14%) of the surgically removed lymph nodes. Size, age and
ultrasonographic findings were not correlated with a higher
risk of malignancy. However, the risk of malignancy was sig
nificantly higher when the LAP was located in the supraclav
icular region than in other cervical regions (p = 0.008). Fine
needle aspiration biopsy was made preoperatively in 27
cases (63%) and revealed five (19%) nodes to be malignant
and 18 (67%) to be due to a reactive cause. The positive
predictive value for benign and malignant cause was 91.3%
and 75% (p = 0.01), respectively.
CONCLUSION: We recommend excisional biopsy if LAP is sus
pected to be malignant or is located in the supraclavicular re
gion. In case of chronic LAP with no obvious infectious cause
or suspected mycobacteria, we recommend fine needle as
piration biopsy as a diagnostic tool. Clinical control and diag
nosing of children with LAP should lie in few, skilled hands.
FUNDING: not relevant.
TRIAL REGISTRATION: not relevant.
Cervical lymphadenopathy (LAP) in children is a common
clinical diagnostic dilemma. The condition has multiple
aetiologies, but the vast majority are caused by benign
disease. However, since LAP can be the first symptom of
an underlying malignant disease, it often causes concern
[1-3].
The cervical region is the most common site for LAP
[3]. Many methods are used to diagnose LAP, but the is
sue of how best to manage LAP in children remains un
clear. Fine needle aspiration biopsy (FNA) is performed
routinely in the evaluation of cervical LAP in the adult
population. In the paediatric population, however, the
use of FNA is not always used as a routine diagnostic
d a n i s h m E d i c a l J O U R NAL 1
procedure and it is not well-described in the literature Original
[4-7]. In children with LAP, clinical symptoms, physical article
evaluation and ultrasonography (US) are often used for Ear, Nose & Throat
assessment. Surgical excision is the golden standard to Department,
diagnose malignancy in cervical LAP [8]. This procedure, Gentofte Hospital
however, requires general anaesthetics and involves a
Dan Med J
risk of nerve lesion, infection, haematoma and other op
2013;60(8):A4667
erative complications.
The aim of our study was to analyse US, FNA, size
and location on the neck to distinguish lymph nodes re
quiring excision from those that do not.
MATERIAL AND METHODS
In this retrospective study, we studied patients who had
excisional biopsies of cervical lymph nodes performed at
the Ear, Nose & Throat (ENT) Department, Gentofte
Hospital, Denmark, in the 2000-2010 period. All patients
aged 0-16 years with cervical lymph nodes were includ
ed. Masses in the thyroid, thyroglossal cysts and
branchial cleft cysts were excluded.
We studied the histology of the removed lymph
nodes and compared results in terms of age, gender, ob
servation time, presentation, location, chest X-ray and
the clinical size of the nodes. Observation time is de
fined as the timespan in days from referral to the ENT
department to surgery. Based on histology reports, we
divided the patients into four groups: Reactive (I), malig
nant (II), granuloma (III) and other (IV). Furthermore, we
compared the results with FNA and US findings.
If the ultrasonic description revealed a round shape,
changes in the hilus, was inhomogeneous or referred as
suspect for malignancy, we classified it as a suspected
malignant diagnosis. The diagnosis was classified as sus
pected reactive if the LAP was described as a normally
shaped and structured, but enlarged lymph node.
We used SPSS to analyse our data. Gender, FNA,
presentation, localisation and ultrasound were calculated
by Fischers exact test. The two sided t-test was used to
compare age, observation time and tumour size with his
tology. A p-value below 0.05 was considered significant.
Trial registration: not relevant.
Results
A total of 43 cervical lymph nodes were excised from 43
children from 2000 to 2010 at Gentofte Hospital, Den
mark.
 2 d a n i s h m E d i c a l J O U R NAL Dan Med J 60/8 August 2013

showing one false negative and two false positive FNAs.

TablE 1
One of the five patients with malignant diagnoses had
Clinical characteristics according to histology (N = 43). no preoperative FNA (Table 1). No complications after
FNA were noted.
Histology
benign malign total p-value A total of 18 (42%) children were examined with US
Age, yrs, mean (SD) 9 (5) 12 (4) 9.5 (5) 0.3 before surgery. The US diagnosis was suspected malig
Gender, n (%) 0.04 nant in five cases; however, four of these were false
Male 27 (96) 1 (4) 28 (65) positive. Three of the histologically verified malignant
Female 11 (73) 4 (27) 15 (35) lymph nodes were examined with preoperative US; two
Observation time, 64 (118) 9 (12) 57 (17) 0.3
were false negatives and one was a true positive. Other
days (SD)
FNA, n (%) 0.01 diagnoses were granulomas, cysts and inconclusive diag
Malign 1 (25) 3 (75) 4 nosis.
Benign 21 (91) 2 (9) 23 LAP presented unilaterally in 26 cases and bilateral
No FNA 16 ly in 17. Unilateral or bilateral affection was not corre
Extension, n (%) 0.6 lated with higher risk of malignancy.
Unilateral 22 (85) 4 (15) 26 (61)
The mean size of the malignant lymph nodes was
Bilateral 16 (94) 1 (6) 17 (39)
Location, n (%) 0.008
2.5 cm and 2.2 cm for the benign (p = 0.7). All malignant
Supraclavicular 2 (40) 3 (60) 5 (12) lymph nodes were 1 cm or above.
Other 36 (95) 2 (5) 38 (88) We found that the malignant lymph nodes size
Size, cm, mean (SD) 2.2 (1.4) 2.5 (1.5) 2.2 (1.4) 0.7 were 1-1.5 cm in the supraclavicular region. In the other
US, n (%) regions, we found that LAP varied from 2 cm to 5 cm.
Malign 4 (80) 1 (20) 5 (28) 0.5
Three out of five malignant lymph nodes were located in
Benign 11 (85) 2 (15) 13 (72)
the supraclavicular region. The risk of malignancy was
No US 25
FNA = fine needle aspiration biopsy; SD = standard deviation;
significantly higher when the LAP was located in the
US = ultrasonography. supraclavicular region than in other cervical regions
(p = 0.008).
Chest X-ray was only made in eight cases; we there
fore excluded this diagnostic tool from further analysis.
The distribution of the histopathological diagnosis is
shown in Table 1. We found that the cause of LAP was of DISCUSSION
reactive origin in 30 patients (70%). Malignancy was the To our knowledge, this is one of the largest studies com
cause in five (12%) of the patients. All patients with ma paring the use of FNA biopsy with excisional biopsy and
lignancy had lymphoma. Granuloma was found in six US for cervical LAP in a paediatric population.
(14%) of the lymph nodes that were surgically removed. Though FNA was the best predictive diagnostic tool
In the lymph nodes containing granulomas, four were to predict malignancy, it rarely provided the final diag
diagnosed with atypical mycobacteria. No cases of LAP nosis in the present study. When lymphoma is suspect
were caused by Mycobacterium tuberculosis. One pa ed, an excisional biopsy remains necessary. However,
tient was diagnosed with Castleman disease and another when the FNA diagnosis is benign and this diagnosis is
with autoimmune lymphoproliferative disease. They compatible with other clinical findings, the method can
were classified as Other. spare this group of patients for surgery. FNA is particu
The mean patient age was 9.5 years (range 1-15 larly suitable in suspected paediatric mycobacterial dis
years) (Table 1). The mean age of patients with malig ease [9]. In line with other studies, we found no compli
nant and benign LAP was 12 and nine years, respectively cations after FNA [1, 9]. Most studies of FNA in children
(p = 0.3). Only one out of 28 boys had malignant LAP. are small, but generally supportive with respect to the
Four out of 15 girls had malignant LAP. This difference use of FNA [4-7]. Although there are no complications
was significant (p = 0.04). to this method, one must consider that this method
The observation time was longer for benign lymph needs very good cooperation between the physician and
nodes (64 days) than for malignant lymph nodes (nine the patient and the parents. Furthermore, it is painful
days) (p = 0.3). and might be traumatizing for the child to undergo the
Preoperative FNA was performed in 27 cases (63%). procedure. The main disadvantage of FNA is the risk of
Five (19%) FNA results suggested malignancy and 18 false negative results. In our study, one patient, who
(67%) reactive cause. We found that the positive was later diagnosed with lymphoma, had a false nega
predictive value for benign cause was 91.3%. The posi tive FNA.
tive predictive value for malignancy was 75% (p = 0.01), The location of the LAP is important. We found that
Dan Med J 60/8 August 2013
Right-sided cervical lymphadenopathy.
the risk for malignancy in patients with LAP in the supra
clavicular region was higher than for patients with LAP
in other cervical regions. This is consistent with other
studies [3]. We found a benign aetiology in the supracla
vicular region as well, both reactive and autoimmune
lymphoproliferative disease.
Surprisingly, we found that US was not as good a
prognostic procedure as we had expected. Contrary to
other studies [10, 11], this method was not a good prog
nostic procedure in our study due to many false positive
and negative results. A possible explanation for this find
ing is that the US was carried out by various physicians,
some of them not specialised in US of the cervical area.
During 2000-2010-period, US was carried out by radiolo
gists at Gentofte Hospital and since then the ENT phys
icians have overtaken this area, but it is clear that more
studies are needed on this matter.
In our study, girls were more often diagnosed with
lymphoma than boys. This is in contrast to the normal
pattern where more boys than girls under the age of ten
have lymphoma [12]. Our small sample size may explain
this unexpected finding.
LAP in children is a common cause for visiting the
doctor. Knowing that the majority are of a benign nature
and not wanting to overlook a possible life-threatening
disease, the doctor therefore faces a difficult diagnostic
dilemma, especially when the lymph node is not sus
pected to be malignant and where there are no obvious
infectious signs. In these cases none of the prognostic
tools are highly sensitive or good enough to use alone.
The physician needs to be aware of the advantages and
drawbacks of the diagnostic tools.
CONCLUSION
In conclusion, lymph nodes in the supraclavicular region
should be considered for excisional biopsy due to a high
risk of malignancy. In case of chronic LAP, which is not
suspected to be malignant and where there is no obvi
ous infectious cause, we recommend FNA as a diagnos
d a n i s h m E d i c a l J O U R NAL 3
tic tool. We found that FNA is a useful tool with no re
ported complications; however, none of the diagnostic
tools were good enough to be used alone, and we rec
ommend excisional biopsy if the lymph node is sus
pected to be malignant. Furthermore, we recommend
that clinical control and diagnosing of children with LAP
lies in few, skilled hands capable of using the clinical in
formation in conjunction with a variety of clinical tools
to make a qualified diagnosis. We suggest a multidiscip
linary team with specialists in paediatrics, ENT, infec
tious diseases and radiology.
CORRESPONDENCE: Maria Ingolfsdottir, re-, nse- og halsafdelingen,
Nordsjllands Hospital, Dyrehavevej 29, 3400 Hillerd, Denmark.
E-mail: harpa_naria@hotmail.com
ACCEPTED: 8 May 2013
CONFLICTS OF INTEREST: Disclosure forms provided by the authors are
available with the full text of this article at www.danmedj.dk.
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